The objective of this project is to study the processing and secretion of calcitonin (CT) and of noncalcitonin secretory peptides, which derive from a common precursor molecule, in a variety of disorders associated with CT hypersecretion such as C-cell hyperplasia, medullary carcinoma of the thyroid (MTC), and other tumors derived from amine precursor uptake and decarboxylation (APUD) cells. Recent studies suggest that human calcitonin is synthesized in the form of a high-molecular weight precursor protein, and is flanked at the amino and carboxy termini by cryptic peptides (CCP) of unknown biological significance. To study the synthesis and secretion of CT and CCP, it is planned to use chemically synthesized CCP to develop a radioimmunoassay (RIA) for this peptide and use this RIA in conjunction with an RIA for CT to investigate the processing or precalcitonin and to determine the presence and levels of circulating CCP in subjects of different sex and age in different pathological conditions characterized by alterations in CT secretion and following administration of calcitonin secretagogues. This would contribute to the detection and management of disorders in which calcitonin hypersecretory is present. (1)